As part of understanding the homeostatic regulation of growth in cells, tissues, and organs, I will continue my studies on the biochemical regulation of cell proliferation and differentiation in normal and abnormalepidermis. The epidermal or skin in vivo stimulants and inhibitors of mitotic activity, DNA synthesis, and other stages in the cell cycle will be studied, identified, and characterized. These findings will be extrapolated to the abnormal epidermis (e.g. Psoriasis) in order to better understand the biochemical basis of skin disease and suggest rational therapy for skin disease. In attempting to relate proliferation to differentiation, the special case in which both hyperkeratinization and the stimulation of arginase activity occur in the epidermis will be studied. Methods: 1. Epidermal extracts (chalone) will be prepared from epidermis isolated from newborn mouse skin. 2. Activity of the extract and its most purified products will be assayed by their action on either DNA synthesis, mitosis, or protein synthesis on target tissue in vitro and in vivo. 3. Autoradiography will be used when necessary to complement findings as to inhibitory action of extracts. 4. Extracts will be purified by combination of alcohol precipitation, membrane filtration and column chromatography. 5. Chemical and physical properties of the purified extract will be determined. 6. Hyperkeratinized epidermis will be assayed for arginase activity and correlations made between epidermal cell layer, arginase activity, proliferation and differentiation.